1/34. Spinocerebellar ataxia type 7 (SCA7) - correlations between phenotype and genotype in one large Belgian family.Spinocerebellar ataxia type 7 (SCA7), in which the degenerative process also affect the retina, belongs to the category of the autosomal dominant cerebellar ataxia type II (ADCA II). We have described the neuropathology of this condition [Martin JJ, Van Regemorter N, Krols L, Brucher JM, de Barsy T, Szliwowski H, et al. On an autosomal dominant form of retino-cerebellar degeneration: an autopsy study of five patients in one family. Acta Neuropathol (Berl) 1994;88:277-286] in a very large Belgian family (CA-1). We have observed anticipation in the age of onset with increasing severity of the symptoms in consecutive generations. The SCA7 gene was mapped to chromosome 3p12-13 [David G, Abbas N, Stevanin G, Durr A, Yvert G, Cancel G, et al. Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat Genet 1997;17:65-70; Del-Favero J, Krols L, Michalik A, Theuns J, Lofgren A, Goossens D, et al. Molecular genetic analysis of autosomal dominant cerebellar ataxia with retinal degeneration (ADCA type II) caused by CAG triplet repeat expansion. Hum Mol Genet 1998;7:177-186], and the gene identified. SCA7 is a new gene of unknown function that contains an expansion of CAG repeats in SCA7 patients. During the procedure of positional cloning, we examined 26 patients belonging to the CA-1 family and realized, in some of them, an ophthalmologic examination and neuro-imaging of the brain. This allowed us to differentiate four groups: (1) asymptomatic young carriers with 38 to 43 CAG repeats; (2) mildly symptomatic, older patients with 38-41 CAG repeats; (3) patients with the full-blown picture of SCA7 and age of onset during adolescence, with 54-55 CAG repeats; (4) children with early onset and rapid fatal course of the disease who had over 55 CAG repeats. We were able to draw correlations between clinical phenotype, age at onset and CAG repeat number and to make predictions, to some extent, as to the clinical course of the disease in new patients.- - - - - - - - - - ranking = 1keywords = family (Clic here for more details about this article) |
2/34. Identification of SCA2 mutation in cases of spinocerebellar ataxia with no family history in mid-eastern sicily.Differential diagnosis between autosomal dominant cerebellar ataxia type I (ADCA I) and idiopathic cerebellar ataxia type P (IDCA-P) is very difficult given only clinical and neuroradiological data. The only certain distinctive characteristic is the presence or absence of family history. We observed 7 patients with late-onset cerebellar ataxia associated with other non-cerebellar signs and without a family history of the disease in which clinical signs were comparable to symptoms found in SCA2. The neuroradiological study showed olivopontocerebellar atrophy in all patients and the presence of hyperintensity of the transverse pontine fibers in 6 patients (85. 6%); molecular analysis showed SCA2 mutations in 2 patients. We also report the case of a patient who was initially considered as IDCA-P but who was later correctly identified as SCA2 with an atypical family history (false IDCA-P), after a genetic mutation was found and following an interview with the mother. Our data suggest that spinocerebellar ataxia syndrome should be defined as idiopathic not only after having excluded the possible symptomatic causes but also in the absence of family history, after having excluded the presence of genetic mutation. We believe that family history, in late-onset spinocerebellar ataxia, cannot be considered as the differential criterion among hereditary (ADCA-I) and non-hereditary (IDCA-P) forms; molecular analysis is required for a correct diagnosis.- - - - - - - - - - ranking = 1.2857142857143keywords = family (Clic here for more details about this article) |
3/34. Sisters homozygous for the spinocerebellar ataxia type 6 (SCA6)/CACNA1A gene associated with different clinical phenotypes.Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease caused by a CAG repeat expansion in the CACNA1A gene. The neurodegeneration that occurs in CAG repeat diseases is considered to share a common mechanism that may result in the gain of a toxic function related to the expanded polyglutamine tracts. However, the phenotypic expression in homozygotes for CAG repeat diseases has been controversial, and is not clearly related to a gain of functional mechanism. We identified a Japanese family with two sisters who were homozygous for the SCA6 with identical CAG repeat expansion (25/25). They showed an earlier age of onset (27 years in both) than their father (44 years), a heterozygote with an expanded allele showing the same CAG repeat length as the homozygotes (25/14). Interestingly, the two sisters showed differences in disease progression and severity, although the age of onset and CAG repeat length were identical. These findings strongly suggest that the gene dosage influences the age of onset, but other unknown factors are also important in the phenotypic expression of homozygous SCA6.- - - - - - - - - - ranking = 0.14285714285714keywords = family (Clic here for more details about this article) |
4/34. Spinocerebellar ataxia type 2 with parkinsonism in ethnic Chinese.OBJECTIVE: To describe the clinical and molecular genetic analysis of a large family of northern Chinese descent with a mutation at the SCA2 locus causing carbidopa-levodopa-responsive parkinsonism. BACKGROUND: Most causes of parkinsonism remain unknown. However, molecular genetic analysis of families with parkinsonism has recently identified five distinct loci and pathogenic mutations in four of those. Additionally, some of the spinocerebellar ataxia syndromes (SCA), particularly Machado-Joseph syndrome (SCA3), are known to cause parkinsonism. Spinocerebellar ataxia type 2 (SCA2) has not previously been described as causing a typical dopamine-responsive asymmetric PD phenotype. methods: A large family was evaluated clinically and molecularly for apparent autosomal dominant parkinsonism. RESULTS: The phenotype includes presentation consistent with typical dopamine-responsive parkinsonism. Other presentations in this family include a parkinsonism/ataxia phenotype, which is classic for SCA2 and parkinsonism, resembling progressive supranuclear palsy. CONCLUSIONS: patients presenting with a family history of parkinsonism, including familial progressive supranuclear palsy and PD, should be tested for the spinocerebellar ataxia type 2 expansion.- - - - - - - - - - ranking = 0.57142857142857keywords = family (Clic here for more details about this article) |
5/34. Asymptomatic CTG expansion at the SCA8 locus is associated with cerebellar atrophy on MRI.Spinocerebellar ataxia type 8 (SCA8) is the first example of dominantly inherited ataxia reported to be caused by a dynamic mutation of the untranslated CTG trinucleotide repeat. We performed genetic and clinical analyses of a family with an isolated case with young onset cerebellar ataxia carrying an expanded 95 CTA/CTG repeats, and revealed that the asymptomatic father was also carrying a much greater expansion of 136 repeats. This paternal transmission developed a large contraction of -41 CTG repeats. The ataxia patient showed almost pure cerebellar symptoms, and a cerebral MRI of the patient demonstrated significant atrophy of the cerebellar vermis and hemispheres with preservation of brainstem and cerebrum. Although the father did not show any neurological abnormalities, his MRI demonstrated mild atrophy of the cerebellar hemispheres. The genetic phenomenon on this family has not been observed in other types of SCAs, and this reduced penetrance may cause reproduction of sporadic SCA8 frequently. Therefore, we must perform careful interviews regarding family history, and suggest the genetic and neuroradiological investigations on family members when we encounter a sporadic patient with the CTG expansion at the SCA8 locus.- - - - - - - - - - ranking = 0.59590470019516keywords = family, family member, member (Clic here for more details about this article) |
6/34. Clinical features and genetic analysis of a new form of spinocerebellar ataxia.BACKGROUND: The autosomal dominant cerebellar ataxias (ADCA) are a clinically heterogeneous group of disorders. The mutations for SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, and SCA-12 are identified and caused by an expansion of a CAG or a CTG repeat sequence of these genes. Six additional loci for SCA4, SCA5, SCA-10, SCA-11, SCA-13, and SCA-14 are mapped. The growing heterogeneity of the autosomal dominant forms of these diseases shows that the genetic etiologies of at least 20% of ADCA have yet to be elucidated. methods: The authors ascertained and clinically characterized a four-generation pedigree segregating an autosomal dominant phenotype for SCA. Direct mutation analysis, repeat expansion detection analysis, and linkage analysis for all known SCA loci were performed. RESULTS: Direct mutational analysis excluded SCA1, 2, 3, 6, 7, 8, and 12; genetic linkage analysis excluded SCA4, 5,10, 11, 13, and 14, giving significant negative lod scores. Examination of the family showed that all affected members had gait ataxia and akinesia with variable features of dysarthria, hyporeflexia, and mild intellectual impairment. eye movements were normal. head MRI showed atrophy of the cerebellum without involvement of the brainstem. In 10 parent-child pairs, median onset occurred 10.5 years earlier in offspring than in their parents, suggesting anticipation. CONCLUSION: This family is distinct from other families with SCA and is characterized by cerebellar ataxia and extrapyramidal signs.- - - - - - - - - - ranking = 0.2877823762412keywords = family, member (Clic here for more details about this article) |
7/34. A novel autosomal dominant spinocerebellar ataxia (SCA16) linked to chromosome 8q22.1-24.1.OBJECTIVE: To characterize a distinct form of autosomal dominant cerebellar ataxia (ADCA) clinically and genetically. BACKGROUND: ADCAs are a clinically, pathologically, and genetically heterogeneous group of neurodegenerative disorders. Nine responsible genes have been identified for SCA-1, -2, -3, -6, -7, -8, -10, and -12 and dentatorubral-pallidoluysian atrophy (DRPLA). Loci for SCA-4, -5, -11, -13, and -14 have been mapped. methods: The authors studied a four-generation Japanese family with ADCA. The 19 members were enrolled in this study. The authors performed the mutation analysis by PCR and a genome-wide linkage analysis. RESULTS: Nine members (five men and four women) were affected. The ages at onset ranged from 20 to 66 years. All affected members showed pure cerebellar ataxia, and three patients also had head tremor. head MRI demonstrated cerebellar atrophy without brain stem involvement. The mutation analysis by PCR excluded diagnoses of SCA-1, -2, -3, -6, -7, -8, and -12 and DRPLA. The linkage analysis suggested linkage to a locus on chromosome 8q22.1-24.1, with the highest two-point lod score at D8S1804 (Z = 3.06 at theta = 0.0). The flanking markers D8S270 and D8S1720 defined a candidate region of an approximately 37.6-cM interval. This candidate region was different from the loci for SCA-4, -5, -10, -11, -13, and -14. CONCLUSION: The family studied had a genetically novel type of SCA (SCA-16).- - - - - - - - - - ranking = 0.29191855729503keywords = family, member (Clic here for more details about this article) |
8/34. Spinocerebellar ataxia--type 6.Fifty six years lady presented with pure cerebellar ataxia with positive family history from paternal side presented to our clinic. dna screening found to be SCA6. This is the first case report of SCA6 from india.- - - - - - - - - - ranking = 0.14285714285714keywords = family (Clic here for more details about this article) |
9/34. Spinocerebellar ataxia type 6 and episodic ataxia type 2 in a Korean family.Spinocerebellar ataxia type 6 (SCA6), episodic ataxia type 2 (EA2) and familial hemiplegic migraine (FHM) have been known as allelic disorders, which are caused by the alteration of the alpha1A voltage-dependent calcium channel subunit. Expansions of the CAG repeat in the CACNA1A gene on the short arm of the chromosome 19 induce SCA6, and point mutations in the same gene are responsible for EA2 and FHM. In recent studies, both SCA6 and EA2 have been concurrently found in families with 26 CAG repeats without previously reported point mutations either in coding sequences or in intron-exon junctions. We describe a Korean family with CAG26 repeats in the CACNA1A gene. Some of the affected family members had progressive ataxia typical of SCA6 whereas others had episodic vertigo responsive to acetazolamide typical of EA2. Our family support that SCA6 and EA2 are allelic disorders with a high phenotypic variability.- - - - - - - - - - ranking = 1.0244761287666keywords = family, family member, member (Clic here for more details about this article) |
10/34. Autosomal dominant palatal myoclonus and spinal cord atrophy.We report a new family with palatal myoclonus, pyramidal tract signs, cerebellar signs, marked atrophy of the medulla oblongata and spinal cord, and autosomal dominant inheritance. These findings were almost identical with those in patients previously reported to have histopathologically confirmed adult-onset alexander disease. Recently, heterozygous point mutations in the coding region of glial fibrillary acidic protein (GFAP) in patients with an infantile form of Alexander disease have been reported. We found a new heterozygous amino acid substitution, Val87Gly in exon 1 of GFAP, in the affected individuals in this family but not in 100 spinocerebellar ataxia (SCA) patients and 100 controls. Therefore, this family might have new clinical entities related to adult-onset alexander disease and GFAP mutation.- - - - - - - - - - ranking = 0.42857142857143keywords = family (Clic here for more details about this article) |
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